miR-4465调控EZH2的表达抑制胃癌细胞增殖、侵袭和迁移的机制探讨  

Study on the mechanism of miR-4465 suppresses the proliferation,migration and invasion of gastric cancer cells by regulating the expression of EZH2

作　　者：郑华山 陈成辉 蔡亲平 林献科 李合 ZHENG Huashan;CHEN Chenghui;CAI Qinping;LIN Xianke;LI He(Donghu Surgery,the Second Affiliated Hospital of Hainan Medical College,Hainan Haikou 570100,China;General Surgery,the First Affiliated Hospital of Hainan Medical College,Hainan Haikou 570102,China)

机构地区：[1]海南医学院第二附属医院东湖外科,海南海口570100 [2]海南医学院第一附属医院普通外科,海南海口570102

出　　处：《现代肿瘤医学》2022年第1期22-27,共6页Journal of Modern Oncology

基　　金：海南省重点研发计划(编号:812201)。

摘　　要：目的:探讨miR-4465通过调控EZH2的表达对胃癌细胞增殖、侵袭和迁移的影响。方法:qRT-PCR检测胃癌组织和细胞系中miR-4465的表达水平;在MKN45细胞中过表达miR-4465或沉默EZH2,采用CCK-8和Transwell检测MKN45细胞增殖活力、迁移和侵袭能力;Western blotting检测EZH2、E-cadherin、N-cadherin和Vimentin的表达情况;双荧光素酶报告基因检测miR-4465与EZH2的相互作用。结果:与癌旁组织相比,miR-4465在胃癌组织中的表达降低,在胃癌细胞系(MCC-803、SGC7901、MKN45)中的表达水平显著低于人永生化胃细胞RGM-1,且在MKN45细胞系中的表达低于其他细胞。过表达miR-4465明显抑制MKN45细胞增殖、迁移、侵袭和上皮间质转化(epithelial-mesenchymal transition,EMT);双荧光素酶报告基因结果证实,miR-4465直接靶向作用于EZH2的3'-UTR;进一步实验证明,同时沉默miR-4465和EZH2能够恢复沉默EZH2对MKN45细胞增殖、侵袭、迁移和EMT的抑制作用。结论:miR-4465通过靶向下调EZH2的表达抑制胃癌细胞生物学行为,miR-4465可能是胃癌治疗的分子靶标。Objective:To investigate the effect of miR-4465 on the proliferation,migration and invasion of gastric cancer cells by regulating the expression of EZH2.Methods:qRT-PCR was applied to detect the expression level of miR-4465 in gastric cancer tissues and cell lines.Overexpression of miR-4465 or silencing of EZH2 in MKN45 cells,and the proliferation,migration and invasion of MKN45 cells were detected by CCK-8 assay and Transwell assay.Western blotting was used to detect the expression of EZH2,E-cadherin,N-cadherin and Vimentin.The interaction between miR-4465 with EZH2 was verified by dual-luciferase reporter gene.Results:Compared with the adjacent tissues,the expression level of miR-4465 in gastric cancer tissues was decreased,and the expression level in gastric cancer cell lines(MCC-803,SGC7901,MKN45)was significantly lower than that in human immortalized gastric cell RGM-1,and the expression in MKN45 was lower than other cells.Overexpression of miR-4465 significantly inhibits the proliferation,migration,invasion and epithelial-mesenchymal transition of MKN45 cell.Dual-luciferase reporter gene result confirmed that miR-4465 was directly targeted with the 3'-UTR of EZH2.Further experiments showed that simultaneously silencing miR-4465 and EZH2 could restored the inhibitory effect of EZH2 silencing on the proliferation,invasion,migration and EMT of MKN45 cells.Conclusion:miR-4465 is inhibit the biological behavior of gastric cancer cells via targeting EZH2.miR-4465 may be a molecular target for the treatment of gastric cancer.

关 键 词：miR-4465 EZH2 胃癌 增殖 迁移 侵袭 

分 类 号：R735.2[医药卫生—肿瘤]